131

Effect of Valproic Acid on Biogenesis and Function of Liver Mitochondria Kiyoshi Hayasaka, MD, Iku Takahashi, MD, Yasuko Kobayashi, MD, Kazuie Iinuma , MD, Kuniaki Nari­sawa, MD and Keiya Tada, MD Department of Pediatrics, Tohoku University School of Medicine, Sendai, Miyagi (KH, IT, KI, KN, KT); Department of Pediatrics, Akita University School of Medicine, Akita (YK)

Valproic acid (VPA: N-dipropylacetic acid) is a com­monly used anticonvulsant but it may cause a Reye­like syndrome , hyperammonemia and hyperglycinemia. Previously we reported that VPA was found to have an inhibitory effect on the glycine cleavage system located in mitochondria on its administration to rats . We have now studied the effects of valproate on the biogenesis and function of liver mitochondria.

Wister strain male albino rats were subcutaneously given 66.4 mg per 100 g body weight per day of VPA (test group) or 0.9% NaCl (control group) for 5 days. Mitochondria were prepared essen tially by the method of Schneider and Hogeboom.

Administration of VPA to rats increased the liver mitochondrial protein within 5 days concomitant with the appearance of enlarged mitochondria. There were no significant differences between the control and VPA-treated rats in liver wet weight. liver protein or liver DNA. The liver mitochondria of VPA-treated rats showed low specific activities of membrane-bound enzymes including monoamine oxidase (65% of con­trol), succinate dehydrogenase (79 '70 of control) and cytochrome oxidase (70% of control). Compared to these membrane-bound enzymes, there were no changes in the activities of matrix enzymes such as glutamate dehydrogenase and NAD+-specific isocitrate dehydrogenase. The liver mitochondria of VPA­treated rats also showed a decreased content of cytochrome a-a 3 (71 % of control) , and decreased res­piration in state 3 (83% of control) and in state 4 (72% of control). The results of in vitro studies on amino acid incorporation suggested a decrease in pro­tein synthesis in the liver mitochondria from VPA­treated rats.

Prolonged administration of VPA seems to impair the mitochondrial structure and function. Many pa­tients can tolerate VPA therapy without problems, even if there are mitochondrial changes in the liver. However, if the biogenesis of liver mitochondria is impaired for any reason, or if the patient cannot metabolize VPA normally and metabolites accumu­late, Reye syndrome or hepatic failure may result.

Key words: Valproic acid, enlarged mitochondria, Reye syndrome.

132

A Case of Immunosuppressive Measles Encepha­lopathy Eiko Mimata , MD, Takanobu Ishihara, MD and Teru­yuki Ogawa, MD Department of Pediatrics, Medical College of Oita, Hazama-cho, Oita

Since Pullan et al (1976) described two cases with measles that resulted in encephalitis, which resembled neither acute measles encephalitis nor SSPE , and called it immunosuppressive measles encephalopathy (lSME) , approximately thirty similar cases have been reported . However, there were no cases in Japan, but have we reported a case considered to be ISME.

The patient was a 3-year-old boy who had develop­ed acute lymphocytic leukemia at the age of two years and one month , and who remained well on mainte­nance therapy after a complete remission had been obtained with chemotherapy. A t the age of three years and one month, he developed measles. About four weeks after recovery, he was readmitted because of attacks of vomiting with deviation of the eyes to the left and ataxia. Thereafter, he deteriorated rapidly with progressive ataxia, generalized convulsions, right hemichorea-like involuntary movement, left hemipare­sis, visual disturbance, continuous rhythmic myo­clonus and confusion .

As to laboratory findings, the serum immunoglobu­lin levels were within normal limits, whereas multiple delayed skin tests were all negative and the lympho­cyte transformation response to Con-A was low. The serum measles antibodies were initially not detectable , but 8 months later the titers had risen to 1:256 by C1-' and 1:8 by HI. The CSF showed initially slight pleo­cytosis (15/cmm) with consistently normal protein levels, while the contents of ,,(-globulin and IgG mark­edly increased to 41 % and 12.4 mg/dl, respectively. In addition, IgM and pligoclonal IgG band were detected. Measles antibodies in the CSF were not detectable at first , bu t 8 months la ter the titers had risen to 1: 8 by CF and 1: 2 by HI. EEG showed con­tinuous high voltage slow waves. CT scanning of the brain showed multifocal low density areas and brain atrophy at two months after the onset.

The ISME features in the literature can be sum­marized as follows: (1) the patients are in an immuno­suppressive state; (2) there is a shorter latent period and a more rapid course than in SSPE; (3) there is no characteristic EEG pattern; (4) there are lower measles antibody titers than in SSPE; and (5) patho­logically the brain showes variable degrees of necrosis and relatively little inflammatory reaction associated with intranuclear inclusions in the neurons and glial cells.

Although in our case the pathological fmdings have not been demonstrated and the course has been so slowly progressive that this patient is still alive after more than one year , it seems to be valid to diagnose our case as ISME according to the clinical findings.

Key words: Immunosuppressive measles encepha­lopathy, SSPE, ALL, intranuclear inclusions.

Brain & Development, Vol 8, No 2, 1986 173

133

Renal Function and Serum Uric Acid Levels in Reye Syndrome with Descriptions of Two Cases Complicated by Acute Renal Failure Kazutoshi Nakano, MD, Yutaka Awaya, MD, Masako Shinozaki, MD and Yukio Fukuyama, MD Department of Pediatrics, Tokyo Women's Medical College, Tokyo

The elevation of blood urea nitrogen (BUN) in Reye syndrome (RS) has been pointed out from time to time, and about 10 cases of Reye or Reye-mimicking syndrome (RMS) with acute renal fa ilure have been reported in the literature . The present report deals with the evaluation of renal function and seru m uric acid (S U A) levels in 16 cases of RS or acu te encepha­lopathy , together with a presentation of 2 cases with aeu te renal failure.

Subjects and Methods The subjects were 16 cases of RS or acute encepha­lopathy or RMS 00 males and 6 females, ranging in age from 9 moths to 6 years old) , who were observed in our department over the period of 1980 to 1984. We mainly observed the changes in BUN , crea tinine, SUA and transaminase in the acute stage in these cases, and com pared the patterns of the changes. We also compared the peak levels of SUA and BUN with the clinical stages classified according to Lovejoy' s criteria .

Results and Conclusion The SUA and BUN levels were high on admission and decreased to the normal ranges within the first six days after the onset of the disease in all cases. The peak levels of SUA, BUN and serum creatinine were observed on the 2nd day of illness in most cases, while those of SGOT and S-CPK were noticed mostly on the 4th day of illness, and those of S-LDH usually at later times. The days of illness on which SUA, BUN and creatinine reached their peak values were significantly earlier than those in the case of LDH , as judged by the T-test method (p < 0.05). Abnormally high levels of SUA (> 5.0 mgjdl), BUN ( > 20 mg/dl) and creatinine (> 1.0 mg/dl) were found in 82.3%, 68.8% and 37.5% of the cases, respectively. This suggests that SUA may undergo one of the earliest biochemical changes in RS or acute encephalopathy, and that SUA elevation is not merely the result of renal failure. A sta tistically significant difference was found between the peak SUA levels in the cases at stage II and those at stage IV (p < 0.025), and also between those at stages II and V (p < 0.05). As to the peak levels of BUN, a statistically significant difference was also found between the cases at stages III and V « 0.05). These results suggest that SUA and BUN would be useful fo r evaluating the severity of disorders and for assessing the prognosis of patients with RS or acu te encephalopathy.

Key words: Reye syndrome, acute encephalopathy, acute renal failure, uric acid.

1 74 Brain & Development, Vol 8, No 2, 1986

134

Correlation between Lactate Levels and Neu­rological Outcome in Hypoxic Encephalopathy and Reye Syndrome Kuniaki Fukuda, MD, Tomoko Goda, MD anti Seikyo Furukawa, MD Department of Pediatrics. National Kagawa Children's Hospital, Zelltsuji, Kagawa

Lactate levels are known as a good indicator of asphy­xia, and to renect depression of cerebral functiuns in Reye syndrome (RS). We measured blood lactate and pyruvate to determine the correlationship between the metabolic abnormali ties and the neurological ou t<.:ome in hypoxic e ncephalopathy (HE) and RS .

Ma terials and Methods We measured bloud lactate and pyruvate in 6 normal controls , 8 patients with HE and 2 patients witlI RS . The 8 patients with HE were divided intu two groups according to the severity of the condition (mild group; 4 patients, severe group; 4 patients). Bloud was col­lected from the patients with HE within 6 hours afte r the onset of illness.

Results 1) There were no neurological abnormalities in the

mild group with H E at one year after the hypox ic illness. In the severe group, two patients died during the acute phase and two patients became rigospastic quadroplegic. One pat ient with RS re­covered wi thout any neurologica l abnormality We could not evaluate the other patient, because she had severe neurological handicaps before this study.

2) Blood lactate values in each group were as fo llows: control group; 11.58 ± 2.70 mg/dl , mild HE; 25.25 ± 6.42 mgjdl, severe HE; 127.68 ± 45.80 mg/dl, and RS ; 21.1 and 59.8 mg/dl.

3) Blood pyruvate va lues in each group were as fo l­lows: ~ontrol group; 0.67 ± 0.19 mgjdl , mild HE; 1.15 ± 0.67 mgjdl. severe HE ; 2.38 ± 1.11 mgjdl. and RS ; 0.8 and 1.8 mgjdl.

4) Blood LIP ratios in each group were as fo llows: control group; 18.9 ± 7.3 , mild HE; 27.0 ± 8.7. severe HE; 62.8 ± 19 .8, and RS; 15.1 and 33.2.

5) Significant co rrelations were observed between the lacta te va lues and pH and BE, respectively.

6) Blood lactate values in one patient with RS de­creased soon aftcr high dose barbitura te and hyper­ventilation therapy. CSF lactate values decreased three days after the reduction of blood lactatc.

Conclusion 1) Blood lac tate levels are a good indicatur for pre­

dicting the neurological outcome in hypox ic en­cephalopat hy.

2) Monitoring of blood and CSF lactate is va luable during high dose barbiturate treatment in Reye sy ndrome.

Key words: Lactate, hypoxic encephalopathy, Reye syndrome.

135

A Study of Serial CT Findings in Acute En­cephalopathy Including Reye Syndrome, with Particular Reference to Cases with Symmetrical Low Density Areas in the Thalami Yutaka Awaya, MD, Kyoko Hirasawa, MD and Yukio Fukuyama, MD Department of Pediatrics, Tokyo Women's Medical College, Tokyo

The purpose of this study is (A) to elucidate the dlung of CT findings from acu te to convalescent stage in acute encephalopathy of obscu re origin (Lyon 1961) (AE) and (B) to analyze the rare cases with symmetrical low density areas (LDA) ir, the thalami o n CT in AE.

A) Subjects and Methods The subjects were 20 infants and children with AE who were admitted to our department during the period of 1980 to 1984. We used Lovejoy's criteria for the severity of consciousness disturbance in the acute stage of AE.

Results I) The brain edema findings 011 CT were positive in

74'/{ of the cases in the acute stage. As the severity acco rding 10 Lovejoy incrcsed from I (mild) to V (severe), so the degree of brain edema became more severe.

2) Twelve case (67 '!c ) showed LOA in the acute stage. T he location of the LOA was mainly diffuse in wh.ite matter, except for one case with multiple lesitJl1s including bilateral thalami and cerebellar denratcs.

3) In the convalescent stage, brain atrophy was seen in 75 7<; of the cases.

4) The transition from brain edema to brain atrophy seen on CT was observed from the 10tlt to 25 th hosp ital day.

B) Subjects Two personal and 7 Iiteratural cases of AE with LOA in the bilateral thalami.

Results 1) We found one case of clinica l RS with multifocal

LDA as mentioned above and one exanthema subitum encephalitis case with typical symmetrical LOA in the thalami. The frequency of this group was only 5% in our AE series. The CT findings of the latter case were as follows: On the 1st hospital day, LOA was negative. On the 3rd day , LOA was visualized in the bilateral thalami; and on the 11 th day , the LOA had disappeared. However , a small high density spot was seen on enhancement in the bilateral thalami. At the 39th day , the LOA was visualized clearly again, and at the l40th day , it had become smaller. These findings suggested to us the process of hemorrhagic infarction.

2) We summarized 2 personal cases and 7 cases in the literature. The 9 cases composed of 5 clinical RS, 3 AE and one encephalitis. All cases had severe consciousness disturbance and all but one had a poor prognosis. The foci of LOA were the bilateral thalami in all cases, and bilatera l cerebellar den-

tates in 2/ 3 of the cases. LOA was continuously seen from the early acute stage to the convalescent stage in almost all cases. We proposed that the etiology of one type of this group was spasms of the basilar artery to the lenticulostriate artery.

Key words: CT scan, acute encephalopathy of obscure origin, Reye syndrollle, thalamus, low density area.

136

Acute Encephalopathy and Reye Syndrome : An Epidemiology , Clinical and Prognostic Study Yoichiro Yamaguchi, MD, Yuko Shiotsuki, MD, Etsuo Otaki, MD, Yukihiko Katafuchi, iUD, To)'ojiro Matsu­ishi, MD alld Fumio Yamashita , MD Department of Pediatrics, Kunlllle Ulliversitv Medical Center, Kurum e, Fukuoka

During the last 10 years , we have experienced 5 cases of acute encephalopathy of unknown origin who had liver dysfunction. and 25 of Reye syndrome (RS). The RS diagnoses were as follows: definite Reyc sy ndro llle (O-RS) 6, Reye like-syndrome (R-LS) 15, and clinical Reye syndrome (C-RS) 4.

The case definition for RS used in our surveys satisfied the criteria of the Center for Disease Control. D-RS satisfied both the clinical and morphological criteria for RS. But R-LS differed in morphological findings and the C-RS cases had no morphological examinations.

Results Epidemiology : the seasonal distribution showed a winter peak. The peak age incidences varied between the first, second and third years of age. The male to female ratio was 0.43.

Clinical manifes tations: there were higher inci­dences of fever (72%), convulsions (72 %) and vomiting (70%) in RS .

Prognosis: the case fatality rate was 50'ii. for D-RS. In this study we proposed 4 significant findings - (1) a patient' s posture, (2) state of consciousness, (3) EEG findings, and (4) CT findings-which might be very important for the patient's prognosis.

Key words: Reye syndrome, epidemiology, clinical, prognosis.

Brain & Development, Vol 8. No 2, 1986 175

137

Alteration of Immunoglobulin in CSF in Cen­tral Nervous System Infections of Infants and Children- Special Reference to the IgG-, JgM­and IgA-Indexes Kenzo Hamano, MD, Nobuaki Iwasaki, MD, Koichiro Ka washima, MD, Ryo Sumazaki, M D and Yumi Hori­gome, MD Division of Pediatrics, Institute of Clinical Medicine, The University of Tsukuba , Ibaraki (KH, NI. KK, RS); Division of Pediatrics, Tsuku ba Gakuen Hospital, Ibaraki (UH)

Until now it has been know n that IgM and IgA in the CSF increase in cases of purulent meningitis and IgG in the CSF increases later in cases of aseptic meningitis. However, the details a re not clear. We examined the alteration of immun oglobulin in the CSF according to Indexes in cases of cen tra l nervous sy stem infec­tions.

Materials and Methods We studied 22 children of 2 m onths to 9 years of age, including 12 cases of aseptic meningitis. 3 of purulent me ningitis, 2 of cerebellar ataxia, 2 of ot her diseases and 3 normal children . Simultaneo usly, we ob tained serum and CSF fro m these child ren, and we deter­mined albumin, IgG , IgM and IgA by ELIS A methods in 42 sam ples of serum and CSF. From the values ob­tained w e calculated the IgG-, IgM- and IgA-Indexes, and the CSF albumin ratio , and investigated the al­teration of each o f them during t he course of each disease. and the correlation b etween t hese ind exes and routine CSF examination results (white cell count. chlorine and glucose).

Results In the patients with aseptic meningitis the IgG Index increased after the 11 th day from the o nset, the IgM­Index increased in the early stage and the IgA-Indcx did not change during the course. T he C SF albumin­ratio decreased after the 11 th day from the o nse t. In the patients w ith purulent meningitis, the igM- and IgA-lndexes and the CSF albumin-ratio increased after t he 11 th day from the onset. On the o ther h and , in the patients with acute cerebellar atax ia, the IgG- and IgM-Indexes increased withou t an in crease in the CSF albumin-ratio . The correlation b etween these indexes and CSF routine examination resu lts was not clear.

Conclusion IgM and IgA were produced in CSF fo r longer and more abundantly in purulent meningitis than in aseptic meningitis, and the blood-brain-barrier was more completely destroyed in purulent meningitis . But in acute cerebellar ataxia , igG and IgM were pro­duced in the CSF without the destruction of the blood-brain-barrier .

Key words: Meningitis, IgG-Index, IgM-Index, IgA­Index.

176 Brain & Development, Vol 8, No 2, 1986

138

The Prevalence of Antibodies against Neuro­trophic Viruses in Patients with Neurological Diseases Toshiaki Abe, MD, Chizuru Nonaka, MD, Mikio Hira­iwa , MD, Koji Usll ijima, MD, Kazuhiko Ollmi, MD, Yasuko Fujita, MD and Tomoko Togo , MD Department of Pediatrics, Teikyo University School of Medicine, Tokyo

Since we recent ly ex perienced five patien ts with infantile spasms showing cy tomegalovirus (CMV) shed­ding in the urine. we tr ied to determine w het her or not CMV infec tion of the central n ervous sys tem was responsible for the etiology of the disease. F o r this purpose, we determined the preva lence of anti­bodies aga inst n euro trophic viru ses. such a s CMV. herpes sim plex (HSV). varicella l oster (V ZV). ru bella (RV) and measles (MV) viru ses, in pat ients with neuro logical diseases. The titers of an tibod ies were determined b y t he complement fixation (CF) test in the serum from patients and normal controls wi thout neuro logical diseases. A tendency of higher incidences of the antibodies against all five viruses in patients than in normal co n trols was observed , t here be ing an especially s ignificant higher incidence of the MV anti­body. The prevalence with aging was also st udied. Significant changes were no t found, however, higher values in patients of age O-l y for HSV. VZV and MV were o bserved . Studies on combinations o f these viral antibodies showed signi ficant prevalence in pat ients fo r (HSV + VZV + RV ) and (HSV + VZV + RV + MV). and higher values fo r (HSV + VZV), (HSV + MV). (HSV + VZV + MV ), (CMV + HSV + VZV + RV), (CMV + VZV + RV + MV) and (CMV + HSV + VZV + RV + MV). Amo ng the pa tients. significantly higher values for HSV and MV were found in epileptic patien ts. and for MV in mental retardation patients. The reason f or these differences between pa tients and normal controls is unknown. However , the prese nt study clearly showed tha t these p atients show a higher incidence of these viral infections, regardless o f whether the infections a re acute, repea ted or chronic. Furthermo re, the high incidence of antibody aga in st CMV was not found in neurological patients compared wi th those aga ins t other viruses. But since the inci­dence in epi lep tic pa tients was fairly higher than that in those with me ntal r etardation. there may be some relationship between the etiology of convulsive dis­orders and CMV infection.

(This work was suppor ted in part by a grant f rom the Ministry o f Education (No 59440048)).

Key words: Infantile spasms, cytomegalovirus, anti­body prevalence, neurotrophic virus_

139

Differential Diagnosis of Reye Syndrome Based on Analysis of 2 I Patients with Acute En­cephalopathy Tateo Sugimoto, MD. Naoki Nishida, MD, Man Woo, MD. Taishi Takeuchi, MD, Akihiro Yasuhara, MD, Masaru Kasahara, MD, Yonosuke Kobayashi, MD, Yoshimi Sakane, MT, Kiyoshi Taniuchi, MD, Kiyotaka Murakami. MD and Hiromitsu Nakano. MD Department of Pediatrics, Kamai Medical University, Osaka (TS, NN, MW, TT, A Y, MK, YK); Taniuchi Children's Hospital, Osaka (YS, KT); Nakano Chil­dren's Hospital, Osaka (KM, HN)

During the last 8 years, we have experienced 21 pa­tients with acute encephalopathy who had liver dysfunction in the early phase of the disease, The diagnoses were as follows: Reye syndrome (RS), 1 (group 1) ; Reye-like syndrome (R-LS), 4 (group B); clinical Reye syndrome (C-RS) , 8 (group C); congeni­tal metabolic diseases, 3 (group D); acquired diseases due to defined origins, 5 (group E) .

RS was diagnosed according to the case definition of the Center for Disease Control. R-LS satisfied the clinical entity of RS but differed in morphological changes. C-RS was diagnosed clinically without mor­phological examination. Group D comprised 2 cases with ornithine carbamyl transferase deficiency and 1 with systemic carnitine deficiency. Group E included 4 patients with proven herpes simplex virus encepha­litis and 1 anoxic encephalopathy due to suffocation.

In order to establish the correct diagnosis the fol­lowing tests were found to be essential besides the morphological studies; repeated cerebrospinal fluid examination, determination of serum carnitine and amino acids, and of urinary organic acids and orotate, and ELISA for herpes simplex virus.

Key words: Reye syndrome, acute encephalopathy, childhood, diagnosis.

140

Sequelae of Acute Encephalitis/Encephalopathy with Special Reference to Postencephalitic Epilepsy Mieko Yoshioka. MD, Shigekazu Kuroki, MD, Hide­yuki Shiraishi. MD and Hideshige Mizue , MD Departmen t of Pediatrics, Kobe General Hospital, Kobe. Hyogo

Among the sequelae of acute encephalitis/encep ha­lopathy, epilepsy is frequent and the seizures are generally intractable. We examined the correlation between clinical and laboratory findings during the acute phase and postencephalitic epilepsy.

Patients and Results We reviewed 54 patients with acute encephalitis ad­mitted to Kobe General Hospital in the ten-year period of 1975-1985, and fo llowed for more than 6 months. They consisted of 34 males and 20 fema les. Three subgroups emerged; group I: cases with se izures after the acute stage (n = 16). group II: cases without seizures who showed EEG seizure discharges after the acute stage (n = 8), and group Ill: cases without seizures who showed no EEG seizure discharges after the acute stage (n = 30). The age of onset ranged from 23 days to 14 years 11 months; mean age, 5 years 5 months. The duration of the follow-up was 6 months to 10 yea rs; 2 years 3 months on average. The infect­ing organism was identified in 19 patients; measles virus in 7 cases, rubella in 6, varicella in one , herpes simplex in 4 and mycoplasma pneumoniae in one. A severe degree of co nsciousness disturbance was found most often in group I. Convulsions in the acute phase were observed in 100% in group I, 88% in group II and 73% in group III, while status epilepticus was found in about half of the patients in group \ and only 23% in group Ill. There was no fixed relationship be­tween the CSF abnormalities and postencephalitic epilepsy. Seizure activities seen on EEG during the acute phase were almost 3 times as frequent in group I and II compared to in group III. The final follow-up EEG showed negative spikes in 75% in group \ , and 100% in group II , but none were seen in group III. General and focal slowing of activity was also found most frequen tly in group I. The types of se izures after the acute phase in group I were 6 cases with generalized tonic-clonic seizures. 2 with Lennox syn­drome , 7 with partial seizures and one with partial seizures in association with an epileptic drop at tack.

Conclusion Convulsions in the acute phase were one of the earliest and most significant prognostic signs of the develop­ment of postencephalitic epilepsy. The control of convulsions during the acute phase, especially statu s epileptics, is most important for the trea tment of ucu te encephalitis.

Key words: Acute encephalitis/encephalopathy, post­encephalitic epilepsy, status epilepticus.

Brain & Development, Vol 8, No 2, 1986 177

141

Acute SSPE and Interferon Therapy Sui Sone, MD, Norio Sakuragawa, MD, Toshiro Kisa, MD, Hiroshi Yoshioka, MD and Masataka Arima, MD Department of Child Neurology, National Musashi Research Institute for Mental and Nervous Diseases, Kodaira, Tokyo (SS, NS); Department of Pediatrics, Shimane Prefectural Central Hospital, Izumo, Shimane (TK); Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto (HY); Division of Mental, Nervous and Birth Defec t Research, National Center for Nervous, Mental and Muscular Disorders, Kodaira, Tokyo (MA )

Acute SSPE usually progresses rapidly and the affect­ed individuals die within 3 months, in spite of any therapeutic trials. We reported a case of acute SSPE who showed the benefic ial effec ts of interferon therapy, recovering from stage III-B (Freeman) to stage II-B.

The patient, a 6-year-old boy , had been healthy until 6 years 2 months of age when he was noticed to have poor coordination , such as unskillful buttoning up . He gradually developed dy scoordination, ataxia, dysphagia and slight character changes in the fo llowing 10 days. Then, he regressed rap idly in the next 20 days to reach a vegetable sta te wi thou t any response to various stimuli , showing a decorticate posture with spastic tetraplegia and hypothalam ic dysfunctio n. He suffered from measles a t one year of age. He was dia­gnosed as SSPE because EEG showed the SSPE co m­plex and the anti-measles Ab titer was elevated in the serum and CSF. On the 33th day from the onset, he was subjected to interferon therapy as follows; intra­venous injection of interferon, 3 x 106 uni ts , daily for one week followed by intrathecal administration of 1 x 106 units daily for the nex t week. After an inter­val of two weeks, daily adminis tration of the same doses intrathecally was performed for 4 days, fo llowed by once-a-week injections fo r t he nex t 9 weeks.

He responded well to this interferon therapy, showing disappearance of the decorticate posture, hypo thalamic dysfunction and dysphagia in the fol­lowing 3 weeks. He began t o react to pain , sound or taste 3 months after the sta rt of this trea tmen t. How­ever, CT scanning demonst ra ted progressive brain atrophy in spite of the uphill course of his clinical co ndition.

This is the first report of the beneficial effects of interferon therapy on acute SSPE. It has not been clarified if a difference between acu te and subacute SSPE may be present in the pathogenesis. However, interferon may be the first choice for treatment of acute SSPE.

Key words: A cute SSPE, interferon therapy .

178 Brain & Development, Vol 8, No 2, 1986

142

Diagnosis of Reye Syndrome : Muscle Biopsy Evaluation Toyojiro Ma tsuishi, MD, Yoichiro Yamagl.lchi , MD, Kenjiro Terasawa, MD, Etsuo Otaki, MD, fkul'a No-naka, MD and Fumio Yamashita, MD . Department of Pediatrics, Kurume University School of Medicine, Kurume, Fukuoka (TM, YY, EO, FY); National Cen ter for Nervous, Mental alld JIll/ SCil laI' Dis­orders, Tokyo (KT, IN)

To determ ine the va lue of a muscle biopsy for the diagnosis of Rcye synd rome, muscle biopsics were performed in I Grade I Reye syndrome case and 9 Reye sy nd rome mimicking cases. A mu scle b iopsy WaS

compared with a liver biopsy in 7 patients. In 3 Reye syndrome mimicking cases, only a muscle biopsy was performed. The fi nal diagnoses in the 10 patie n ts were: Grade I Reye syndrome (N = I) , mitochondrial cytopathy with lact ic acidosis (N = 1) , mitochondrial myopathy (N = 1), sibling cases of system ic carnitine deficiency (N = 2), fulminant hepatitis without jaun­dice (N = 2), drug intoxication (N = I) and recurrent Reye mimicking syndrome (N = 2). Light and electron microscopic studies were performed on liver biopsy specimens. Muscle specimens were obta ined from 10 patients and rout ine histochemical and ultrastructural studies were performed.

Summary Typ ical findings such as fine lipid accumulat ion in type 1 fibers, mitocho ndrial disrup t ion and swe lling were found in Grade 1 Reye syndrome, and ragged red fibers' with marked lipid accumulation were seen the mitochond ria l cy topathy and mitoch ondrial myo­pathy cases, Ultrastructural examination showed the collec tion of num erous vacuoles and the accumulat ion of mitochond ria, which were often abnormal in shape and size. The same findings were observed in the two systemic carnitine deficiency cases, however, the lipid drople ts were larger than in Reye synd rome. Lipid storage and mitochondrial disruption were also no ted in the 2 fulminant hepatitis cases, and one of the re­current Reye syndrome mimicking cases. Nonspecific type 2 fiber atrophy was observed in the drug intox i­cation case and one o f the recurrent Reye syndrome mimicking cases. Therefore, it is difficu lt to make the diagnosis of Reye syndrome on the basis of on ly a muscle biopsy.

Key words: Reye syndrome, mimickers, liver biopsy. muscle biopsy.

143

Circadian Rhythm of Sleep-Waking and Body Temperature (BT) in Cases with Thalamic Le­sions Induced by Acute Encephalopathy Kimiko Tamagawa, MD, Ten/ko Suzuki, MD, Masashi MizugliChi, MD and Kazuhiko Komiya, MD Department of Pediatric Neurology, Metropolitan Neurological Hospital, Fuchu, Tokyo

Recently, several reports have been published concern­ing the unique CT findings in cases of acute encepha­lopathy, Common findings in these cases are sym­metrical low density lesions in the thalami and the cerebellum in an acute stage of the disease. The patho­genesis of these lesions has remained to be solved.

Subjects and Methods The subjects were two girls (2 years 7 months old and 4 years 9 months old), who showed symmetrical low density areas in the thalami and the cerebellum in the course of acute encephalopathy which later developed into severe brain damage. Clinically, they fell rapidly into coma, and exhibited decerebrate rigidity and gen­eralized convulsions, following upper respiratory tract infection or fever and vomiting. Laboratory investiga­tions revealed slightly elevated s-GOT and CPK, but other findings were normal including serum ammonia, blood sugar , pyruvate and lactate. CSF showed a slight elevation in protein content (135 and 94 mg) and opening pressure (200 and 350 mmH,O). CT scanning demonstrated symmetrical low density areas that did not show enhancement with contrast drugs in the thalami and the cerebellum (mainly the dentate nu­clei) shortly after admission. Though these lesions disappeared in one case, in the other they developed into high density lesions in the thalami. Moreover, diffuse cerebral atrophy including the brain stem developed in both cases, The cases were bedridden be­cause of rigido-spastic tetraplegia, and became pro­foundly mentally retarded with abnormal slow eye movements.

Results All day polygraphic studies (EEG, EOG, EMG , ECG, respiration and BT) were performed as to the sleep­waking rhythm and fluctuation of BT. The results can be summarized as follows: 1) A disorder of the circadian rhythm of sleep-waking was observed in both cases. They showed the dispersed type of sleep. 2) There were no specific sleep activities such as vertex sharp transients and spindles, and their sleep stages were simplified. Non-REM sleep was divided into the following three stages: drowsy, fast wave sleep and slow wave sleep, 3) The duration of the REM period decreased in both cases. 4) In one case, rhythmic ac­tivities were continuously observed on EEG during N-REM sleep, 5) The circadian rhythm of BT was maintained in one case, but not in the other.

The above findings seem to indicate that these cases not only have thalamic lesions bu t also lesions in the brain stem and the cerebral cortex, which have fiber connections with the thalamus. Further investigation in these cases may clarify the role of the human thalamus in biological rhythms.

Key words: Circadian rhythm, thalamic lesion , CT scan, acute encephalopathy .

144 An Electrophysiological Study in Cases with Acute Disseminated Encephalomyelitis Yoshihiro Nakagawa, MD, Kouzou Mutoh, MD and Hiroatsu Hojo, MD Department of Pediatric Neurology, Shizuoka Prefec­tural Children's Hospital, Shizlloka

Abstrac t not received.

Brain & Development, Vol 8, No 2, 1986 179

145

Symmetrical Low Density Areas in Bilateral Basal Ganglia in Children with Viral Encepha­litis Junko Ochi, MD, HanlO Hattori, MD, Tatsuya Fujii, MD, Toshin Go, MD, Kenkichi Kataoka, MD, Take­hiko Okuno, MD and Harnki Mikawa, MD Department of Pediatrics, Kyoto University School of Medicine, Kyoto

In viral encephalitis, CT findings may appear non­specific, such as brain edema and subdural f1uid collection. We report two patients with viral encepha­litis (influenza A and measles) in whom CT showed symmetrical low density areas in the basal ganglia bilaterally.

Case 1 : A ten-year-old girl. Five days before ad­mission, she had fever and malaise, and the day before admission, drowsiness. On admission, she was semi­comatose. Involuntary choreoathetoid movements of all 4 limbs were noted. There were no abnormal find­ings in the chest or abdomen. The limbs were flaccid with decreased deep tendon reflexes. Babinski signs were positive bilaterally. EEGs showed theta waves of 6 cis with occasional diffuse delta waves of 1.5-2 cis. CSF showed no increase in cells (2/mm 3

), and protein was 72 mg/dl. IgG 12 mg/dl, myeline basic protein 2.25 ng/ ml and glucose 40 mg/dl. The comple­ment fixation titer for influenza A in the serum was less than 1:4 on the 2nd hospital day , and 1: 32 on the 26th day. Brain CT revealed symmetrical low density areas in the bilateral putamina. Contrast en­hancement was noted around the low density areas.

Case 2: An ll-month-old boy. Three days before admission, he had fever. On the day of admission, he had miliary-sized exanthema and he was drowsy. There were no abnormal findings in the chest or ab­domen. The deep tcndon reflexes were increased. Babinski signs were positive bilaterally. EEGs showed diffuse delta waves of 1.5 cis bilaterally . CSF show­ed no increase in cells (2/mm 3 ), and protein was 22 mg/dl and glucose 62 mg/dl. The serum hemag­glutination titer for measles virus was less than 1:8 on the day of admission, and 1:64 on the 15th day. CT showed symmetrical low density areas in the thalamus b ila terally .

The focal lesions seen on CT appeared to be due to localized inflammation, necrosis or edema. As the low density areas were located bilaterally, vascular infarction may have been caused by increased intra­cranial pressure.

Key words: Symmetrical low density areas, basal ganglia, CT scan, viral encephalitis.

180 Brain & Development, Vol 8, No 2, 1986

146

Three Cases of CNS Disease Associated with Mycroplasma Pneumoniae Infection Susumu !shiyama, MD, Kaorn Togashi, Yoshindo Miura, Kanehiro Konno, MD and Hitoshi Suzuki, MD Department of Pediatrics, Fukushima Medical College, Fukushima

Mycoplasma pneumoniae is a common respiratory pathogen. It usually causes a mild respiratory illness but is capable of producing a wide variety of clinical syndromes.

Three cases of CNS diseases (encep haliti s. menin­goencephalitis and polyradiculoneuritis) following respiratory tract infection by M pneumoniae were presented .

Case 1 An ll-year-old girl had a cough, nausea, arthralgia and abdominal pain prior to admission. On the day of admission she had a high fever and generalized weak­ness. Two days after admission she was stuporous. and the next day she was responsive only to deep pain. EEG showed frontal dominant iJ waves. Two weeks after admission her consciousness returned to normal, but motor fu nction recovery took one month.

Case 2 A 6-year-old boy developed fever and a cough seven days prior to admission to a hospital. He s howed signs of right middle and lower lobe pneumonia , and was given erythr9mycin. He developed bilateral leg weak­ness , and on the fo llowing day he showed arm weak­ness, ptosis of the bilateral eye-lid, and paralysis of the 6th and 7th cranial nerves. Deep tend on ret1exes of the knees and ankles were absent. CSF showed mild albumino-cytologic dissociation. The diagnosis of polyradiculoneritis was confirmed by the clinical and physical findings.

Case 3 An 8-year-old boy developed fever and a cough ten days prior to admission to our hospital. On the day of admission h e became stuporous and developed urinary incontinence. Chest roentgenogram and CSF findings revea led right middle and lower lobe pneu­monia, and meningoencephalitis. His clinical progress was very good, with discharge on the 14th day.

Cultures fo r M pneumoniae from throat swabs and CSF were negative in all cases.

Serum anti-mycoplasma antibody titers (PHA) were elevated in all cases and CF titers in CSF were elevated in cases 2 and 3.

A M pneumoniae infection seems to be very impor­tant in any patients with inflammatory neu rological disorders of unknown etiology.

Key words: Mycoplasma pneumoniae, CNS disease.

147

Two Unique Cases of Herpes Simplex Virus Encephalitis Hiroshi Ushijima, MD, Yasuo Kondo , MD, Kumiko Sugamata, MD, Hiroaki Shiraishi, MD, Mikio Hiraiwa , MD, Chizuru Nonaka, MD, Seiko Fujita, MD, Tomoko Togo, MD, Kazuhiko Ohmi, MD, Toshiaki Abe, MD and Ryoichi Fujii, MD Department of Pediatrics, Teikyo University School of Medicine, Tokyo

Herpes simplex virus encephalitis (HSV£) is important because it is frequently severe and some anti-viral drugs are effective for curing the disease. We present here two unique cases of HSVE ; one had HSV brain stem encephalitis and the other neonatal HSVE.

Case I : A 10-year-old boy had complained of a high fever and headache from the 17th day before admission. Disturbances of writing and walking, left facial palsy, visual disturbance, nystagmus and drowsi­ness developed after admission. Physical examinations showed abnormalities of the brain stem predominantly on the left side, and disorders of the bulbocerebellar tract, pyramidal tract and peripheral roots of cranial nerves. Auditory brain stem response investigation and electronystagmography also showed disturbance of the brain stem. Steroid therapy was started 2 weeks after admission and was effective. Serial examinations of viral antibodies in serum and CSF by means of CF, fluorescence and emzyme-linked immunoassays sug­gested that reactivation of HSV (type I) in nerve cells comprised the etiology of the disease.

Case 2: A one-month-old girl was admitted with poor sucking and hypothermia. S he was born natural­ly after 36 weeks gestation and had a fever on the 15th and 16th days after birth . Muscle hypotonus, hyper-reflexia, a poor sucking reflex and a decreased Moro reflex were noticed. Hepatosplenomegaly and vesicles were not found. Status epilepticus continued fo r 2 days after admission. Brain CT showed remark­ably diffuse high density areas in the white matter , cerebellum and brain stem due to bleeding and calcifi­cation. EEG showed a flat rhythm . The HSV culture was negative. Echovirus (type 22) was cultured from a throat swab. Antibodies to HSV (type 2) and echo­virus (type 22) were present at high levels in blood and CSF . It was suggested that she was infected with HSV during pregnancy and with echovirus after birth. Microcephalus and cerebral palsy developed after discharge. Anti-virus drugs were not used in either case.

Key words: Herpes simplex virus encephalitis.

148

A Case of Leukoencephalopathy Associated with a Mycoplasma Pneumoniae Infection Takahiro Nara , MD, Masako Matoba , MD, Shunsuke Numaguchi, MD, Fumiyuki Ito , MD and Kihei Mae· kawa, MD Department of Pediatrics, The likei University School of Medicine, Tokyo

Neurological diseases associated with a Mycop lasma pneumoniae infection are being reported with in­creasing frequency. This report documents a case of leukoencephalopa thy showing serologic evidence of a Mycoplasma pneumoniae infection.

Case A 9-year-old girl , who had a mild upper respiratory tract illness 10 days prior to admission, developed difficulty in walking and somnolence. A bilateral py­ramidal t ract sign was observed predominantly on the left side . There was no meningeal sign. CSF examina­tion results were normal. Brain CT-scanning was normal , and EEG showed diffuse slow ac tivity. She was diagnosed as having acute encephalopathy. Dex­amethasone and glycerol were administered. Her level of consciousness deteriorated gradually; on the 3rd day she fe ll into a coma with paralysis of the left leg. On the 4 th day , the coma and paralysis appeared to have improved to some extent. She was able to blink on command on the 6th day. The paresis lasted for 30 days. Brain CT-scanning on the II th day showed low density of the white matter especially in the right parietal area. This was improved on the 26th day. Thirty-four days after admission, she was discharged from the hospital with minimal motor deficits. Serum samples showed elevated Mycoplasma pneumoniae complement fixation (CF) titers and cold agglutinin titers, but CSF titers were negative.

Discussion From the clinical and laboratory findings , she was diagnosed as having leukoencephalopathy associated with a Mycoplasma pneumoniae infection. Several kinds of neurological diseases associated with Myco­plasma pneumoniae infections, such as encephalitis, meningitis, polyneuritis and acute cerebellar ataxia have been reported recently, but their pathogenesis has not been clarified. Allergic encephalitis may be strongly related to the Mycoplasma penumoniae in­fection in our cases.

Key words: Leukoencephalopathy, Mycoplasma pneu­moniae.

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149

A Case of Acute Relapsing Disseminated En­cephalomyelitis Yasushi Yoshioka. MD. Toshiko Sakaguchi. MD, Hiro­fumi Fujimoto. MDand Fumihiko Suehiro. MD Department of Pediatrics. Hyogo Prefectural Amaga­saki Hospital, Amagasaki. Hyogo

It is well known that acute disseminated encephalo­myelitis occurs following an infection or a vaccination. but some uncommon cases were reported of acute relapsing disseminated encephalomyelitis (ARDEM) which occurred with no specific et iology and relapses several times.

We reported and discussed a case of ARDEM. This 8-year-old girl was doing well until 1 month before admission when she developed headache and vomiting.

On admission, she was alert and showed no nuchal rigidity, but her pupils were dilated and didn't react to light. DTR was exaggerated. Laborato ry data were as follows: WBC, 11,200; ESR , 52 mm/hr ; and CRP, 1 (+). CSF findings showed mild pleocytosis (60% polymononuc!ear), but the protein and glucose con­centrations were normal. The CSF cu lture was nega­tive. EEG showed irregular slow waves, and CT scanning showed enlarged lateral ventricles.

After admission, she was treated for myeloen­cephalitis with antibiotics, glycerol and dexametha­sone, and recovered completely within 1 week.

A second episode, however, occurred soon after discontinuation of the dexamethasone, but she com­pletely recovered with the use of dexa methasone again. After that she was stable, but about 5 months later she developed a 3rd episode with the onset of left hemiparesis. But it was very mild and subsided with no therapy. For the 3rd episode, CT scanning showed hypodensity in the righ thalamus but a radiologic study of brain vessels showed them to be intact.

During the whole course, we cou ldn' t detect any elevation of the viral titer, and measurement of myelin basic protein showed the normal pattern , but electro­phoresis of serum and CSF indicated d emyelination .

Now she has no neurological deficit in spite of the abnormal CT scan findings, and she is being followed at OPD.

Key words: ARDEM. dexamethasone, CT scan.

182 Brain & Development, Vol 8, No 2, 1986

150

A Case of Multiple Sclerosis with Cardiac Involvement Tatsuya Fujii. MD. Takehiko Okuno, MD. Kenya Nishioka, MD. Haruo Hattori. MD. funko OeM. MD. Toshin Go, MD and Haruki Mikawa. MD Department of Pediatrics, Faculty of Medicine, Kyoto University. Kyoto

We have e ncountered a child with multiple sclerosis who had cardiac symptoms with echocardiographic abnormalities , the appearance of which coincided with exacerbation of the neurological symptoms.

Case Report The patient is a lO-year-old girl who had the first episode of fever, vomiting, headache, visual disturb­ance and le thargy when she was 9 years old. These symptoms continued for about 24 hours but disap­peared the next day. Four months later , she had the same symptoms, which again disappeared the follow­ing day. Two months after the second episode, she experienced the third exacerbation with tetra pareSIS, rectovesical disturbance, nystagmus and Parinaud syndrome in add ition to the previous symptoms. CT scanning showed a low density area with circumfer­ential enhancement in the right temporal lobe. Blood examination revealed an increase in the serum levels of lactic dehydrogenase (LDH) and creatine kinase (CK) , 1,1141U/ L and 659 lUlL, respectively. Isozyme analysis showed an increase in the LDH 1 and CK, levels. T reatment with prednisolone improved her neu­rological symptoms and the serum enzymes decreased to norm al values. After a 3-month remission, she had the fourth relapse, and serum LDH and CK began to increase gradually. When the serum levels of LDH and CK had risen to 2,755 lUlL and 361 lUlL , respective­ly, she complained of chest pain, palpitation and fatigue. Electrocardiography showed ST segment depression in leads II , III and aVF, and an abnormal Q wave in lead aVL. Echocardiography revealed hy­pertrophy of the left ventricular poster ior wall and the interventricular septum . These cardiac symptoms improved spontaneously and the serum enzy mes also became normalized.

At present, the pathogenesis of the cardiac involve­ment in this patient is unknown, but such mechanisms as those speculated for the pathogenesis of the cardiac complication associa ted with central nervous system disorders other than multiple sclerosis may also be in­volved in this pa tien t.

Key words: Multiple sclerosis, electrocardiography . echocardiography. cardiac symptoms.